title: Free light chain content in culture media reflects recombinant monoclonal antibody productivity and quality.
abstract: Monoclonal antibodies (mAbs) are currently the dominant class of biopharmaceuticals. Due to the high dosage requirements of most mAb therapeutics, high productivity and low aggregation are prevailing criteria during cell line generation and process development. Given that light chains (LCs) play an important role in antibody folding and assembly, and that most mAb producing cell lines also manufacture free LCs, we sought to investigate whether there was a relationship between free LC levels in cell culture media and mAb productivity/quality. To this end, a series of analytical methods were developed in order to quantify free LC content in cell culture media and assess mAb productivity and aggregation levels. Afterwards, conditioned media samples from different cell lines at identical culturing conditions and a single clone under varying culturing conditions were analyzed. Higher LC expression was found to correlate with higher cell viability, higher mAb productivity, and lower aggregation. While LC expression cannot yet be definitively considered the root cause of these phenomena, these results are consistent with the role of LCs in mAb production, suggesting that free LC expression levels may potentially serve as a parameter for cell line generation and cell culture process optimization.
authors.affiliation: Dept. of Chemistry, University of Massachusetts Lowell, Lowell, MA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Bhoskar
authors.forename: Brett
authors.initials: B
authors.lastname: Belongia
authors.forename: Robert
authors.initials: R
authors.lastname: Smith
authors.forename: Seongkyu
authors.initials: S
authors.lastname: Yoon
authors.forename: Tyler
authors.initials: T
authors.lastname: Carter
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D016466:CHO Cells; D002470:Cell Survival; D002853:Chromatography, Liquid; D003001:Cloning, Molecular; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000096:biosynthesis; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis*; D013058:Mass Spectrometry; D017510:Protein Folding; D011994:Recombinant Proteins / Q000096:biosynthesis*
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D011994:Recombinant Proteins
keywords: antibody aggregation; antibody productivity; cell culture optimization; clone selection; free light chains